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CHAPTER 10 DISEASES OF ALIMENTARY SYSTEM Department of Pathology, School of medicine ZheJiang University Lai Maode • • • • • Esophagitis Gastritis (acute, chronic ) Peptic ulcer Enteritis(diarrheal diseases ) Gastrointestinal carcinoma Esophagitis Morphology • Three histologic features are characteristic of uncomplicated reflux esophagitis ,although only one or two may be present: (1) eosinophils, with or without neutrophils, in the epithelial layer; (2) basal zone hyperplasia; and (3) elongation of lamina propria papillae. Intraepithelial neutrophils are markers of more severe injury. Clinical Features The dominant manifestation of reflux disease is heartburn, sometimes accompanied by regurgitation of a sour brash. Rarely, chronic symptoms are punctuated by attacks of severe chest pain mimicking a heart attack. The severity of symptoms is not closely related to the presence and degree of anatomic esophagitis. Though largely limited to adults older than age 40, reflux esophagitis is occasionally seen in infants and children. The potential consequences of severe reflux esophagitis are bleeding, development of stricture, and Barrett esophagus, with its predisposition to malignancy Barrett esophagus • Barrett esophagus is apparent as a salmonpink, velvety mucosa between the smooth, pale pink esophageal squamous mucosa and the more lush light brown gastric mucosa. • Microscopically, the esophageal squamous epithelium is replaced by metaplastic columnar epithelium. 图10-1 Barrett食管 食管下段黏膜(距胃贲门5厘米)鳞状上皮为柱状上皮取代(化生),间质有炎细 胞浸润。切片由浙江大学医学院附属第一医院滕晓东医师提供。 Acute gastritis • An acute mucosal inflammatory process. • Accompanied by hemorrhage and by sloughing of the superficial mucosal epithelium (erosion). • An important cause of acute gastrointestinal bleeding. Morphology • 1. Early changes : mucosal congestion and edema. 2. Severe changes: mucosal erosions and hemorrhage • 3. Inflammatory infiltrate Clinical course 1. Asymptomatic 2. Epigastric pain, nausea, vomiting, hematemesis and potentially fatal blood loss. Chronic gastritis Chronic gastritis is marked principally by mucosal chronic inflammatory changes and glandular atrophy with epithelial metaplasia. Etiology and pathogenesis • 1. Autoimmune damage: Autoimmune damage appears to be a major causal factor in type A gastritis. • 2. A variety of mucosal irritants tobacco, alcohol, salicylates, and reflux of biliary secretions. It may be closely correlated with type B gastritis. • 3. Helicobacter pylori Classification and morphology • 1. Chronic superficial gastritis, CSG: • (1) mucosal congestion and edema. • (2) chronic inflammatory cell infiltration (mainly lymphocytes and plasmacytes) in superficial mucosa. • (3) glands keep intact. 2. Chronic atrophic gastritis, CAG: • (1)Glandular atrophy, decrease or loss of specialized secretory cell( parietal cells, chief cells) • (2)Chronic inflammatory cell infiltration and H.pylori-induced proliferation of lymphoid tissue within the gastric mucosa. • (3)Intestinal and pseudopyloric metaplasia. Intestinal metaplasia • Refers to the replacement of gastric epithelium with columnar and goblet cells of intestinal variety. • Gastric intestinal type carcinomas appear to arise from dysplasia of this metaplastic epithelium. The difference between Type A and Type B • • • • • • • • • Type A Type B Location mainly in the corpus in the antrum Gastric secretion severe impair moderate imparir Parietal cell Antibody + intrinsic antibody + Serum gastrin higher lower Associated disease pernicious anemia iron deficiency anemia Autoimmune + endocrine disorders frequent none Malignant change none about 8% • 3. Gastritis verrucosa • 4. Hypertrophic gastritis Clinicopathological correlation • 1. Asymptomatic • 2. Lower gastric acid secretion and decreased secretion of pepsin. • 3. Epigastric discomfort, nausea and vomiting and,in more severe forms, occult bleeding or even massive hemorrhage. • 4. Pernicious anemia • 5. Relation to gastric-peptic ulcer and gastric cancer. 图10-2 幽门螺杆菌 Warthin-Starry银染示幽门螺杆菌呈黑色弯曲棒状(箭头),粘附于胃粘膜(胃小 凹)表面,不侵入固有腺体。细胞核亦为黑色。切片由浙江大学医学院附属第一医 院王丽君医师提供。 图10-3 慢性萎缩性胃炎 Peptic ulcer • Definition • Peptic ulcer is a chronic, most often solitary, lesions that occur in any portion of gastrointestinal tract exposed to the aggressive action of acid-peptic juices. Etiology and pathogenesis • The exact cause of peptic ulcer is still unknown. • 1. Imbalance between acid-pepsin and mucosal resistance. – Increased acid-pepsin secretion, decreased mucosal resistance, or the two actions together are ulcerogenic. • (1) Duodenal ulcers result in the great majority of cases from hyperacidity. • increased number of parietal cells • increased levels of gastrin. • (2) Gastric ulcers are associated with normal or even low gastric acid levels and possibly result from lowered mucosal resistance • bile reflux • gastric mucosal ischemia • 2. Disturbance of neuro-endocrine system: • Emotional factors ---------vagal stimulation • increased in the flow of gastric juice • increased gastrin • 3. H.pylori • HP infection is present in virtually all patients with duodenal ulcers and about 70% of those with gastric ulcers. • Antibiotic treatment of HP infection promotes healing of ulcers and tends to prevent their recurrence. Morphology • Gross appearance: • 1. Shape: round, sharply, punched-out holes in the mucosa. • 2. Size: usually less then 2cm in diameter. • 3. Base: remarkably clean and flat. • 4. Location: the lesser curvature of the stomach. • 5. The mucosal margin not elevated. • 6. The mucosal folds radiating from the crater. Microscopic appearance • 1. Four histological zones of the ulcer floor: • (1) fibrinous exudate mixed with occasional neutrophils and tissue debris. • (2) necrotic tissue • (3) granulation tissue. • (4) fibrous collagenous scar. • 2. Thickened and occasionally thromhosed vessel wall or obliterative endoarteriolitis in scar tissue. • 3. The margins showing chronic gastritis. • 4. Coalescence of the muscularis mucosa with muscularis propria around the ulcer . Clinicopathological correlation • 1. Epigastric pain . – Be worse at night and occurs usually 1 to 3 hours after meals. • 2. Nausea, vomiting, bloating, belching and/or excessive salivation, anorexia and vomiting. • 3. Occult bleeding or massive hemorrhage. Complication • 1. Bleeding • 2. Perforation • 3. Stenosis (obstruction) from edema or scaring of pyloric canal or duodenum. • 4. Malignant transformation. 图10-4 消化性溃疡的成因 图10-5胃消化性溃疡 (大体) 图10-6胃消化性溃疡 (光镜) 溃疡深达肌层,由内而外分四层:(1)炎性渗出物(白细胞、纤维素等);(2) 坏死组织;(3)较新鲜之肉芽组织;(4)肉芽组织移行为陈旧瘢痕组织。 Appendicitis ETIOLOGY AND PATHOGENESIS • Bacterial invasion • Luminal obstruction Classification and Morphology Acute appendicitis 1. Acute simple appendicitis 2. Acute phlegmonous appendicitis 3. Acute gangrenous appendicitis Complication: abscess around appendix acute diffuse peritonitis Chronic appendicitis 图10-7 急性蜂窝织性阑尾炎 Inflammatory Bowel Disease (IBD) • Crohn disease and ulcerative colitis are chronic relapsing inflammatory disorders of unknown origin, collectively known as idiopathic inflammatory bowel disease (IBD), which share many common features. They result from an abnormal local immune response against the normal flora of the gut, and probably against some self antigens, in genetically susceptible individuals. • Crohn disease may affect any portion of the gastrointestinal tract from esophagus to anus but most often involves the ileum; about half of cases exhibit noncaseating granulomatous inflammation. • Ulcerative colitis is a nongranulomatous disease limited to the colon. 图10-8 Crohn病 小肠壁(浆膜)内非干酪样坏死性肉芽肿,由上皮样细胞、多核巨细胞及增生的纤 维母细胞组成,周围有淋巴、浆细胞浸润,肉芽肿中心无干酪样坏死。 图10-9 溃疡性结肠炎 结肠黏膜弥漫性炎细胞浸润,可见隐窝脓肿形成(箭头),并有黏膜表浅糜烂。 Esophageal carcinoma Morphology • Squamous cell carcinomas are usually preceded by a long prodrome of mucosal epithelial dysplasia followed by carcinoma in situ and, ultimately, by the emergence of invasive cancer. Early overt lesions appear as small, gray-white, plaquelike thickenings or elevations of the mucosa. In months to years, these lesions become tumorous, taking one of three forms: • (1) polypoid exophytic masses that protrude into the lumen; • (2) necrotizing cancerous ulcerations that extend deeply and sometimes erode into the respiratory tree, aorta, or elsewhere; and • (3) diffuse infiltrative neoplasms that cause thickening and rigidity of the wall and narrowing of the lumen. Whichever the pattern, about 20% arise in the cervical and upper thoracic esophagus, 50% in the middle third, and 30% in the lower third. Clinical Features • Esophageal carcinoma is insidious in onset and produces dysphagia and obstruction gradually and late. Weight loss, anorexia, fatigue, and weakness appear, followed by pain, usually related to swallowing. Diagnosis is usually made by imaging techniques and endoscopic biopsy. Because these cancers extensively invade the rich esophageal lymphatic network and adjacent structures relatively early in their development, surgical excision is rarely curative. Thus, much emphasis is placed on surveillance procedures for individuals with persistent manifestations of chronic esophagitis or known Barrett esophagus. Esophageal cancer confined to the mucosa or submucosa is amenable to surgical treatment. (1)溃疡型 (2)蕈伞型 (3)髓质型 图10-10 食管癌大体类型 (4)缩窄型 Gastric carcinoma Gastric carcinoma is the most common cause of death in malignant tumors of alimentary system in China. It usually appears in fifth and sixth decade of life. The male-female ratio is approximately 23:1. Morphology • • • • • Location : mainly along the lesser curvature(80.3%) predominantly in the antrum (56.4%) early gastric cancer: The cancer have not invaded the muscularis propria and are therefore limited to the mucosa and submucosa. Gross appearance • • • • Early gastric cancer: 1. Protruded (Ⅰ) type 2. Superficial (Ⅱ) type 3. Excavated (III) type • • • • Advance gastric carcinoma : 1. Polypoid or fungating type 2. Ulcerative type 3. Infiltrating type (1)息肉型或蕈伞型 (2)溃疡型 (3)浸润型 图10-12 进展期胃癌大体类型 Tumor of the small and large intestines • Non-neoplastic (Benign) Polyps:Hyperplastic polypsHamartomatous polyps Juvenile polyps Peutz-Jeghers polypsInflammatory polypsLymphoid polyps • Neoplastic Epithelial Lesions:Benign polyps Adenoma*Malignant lesions Adenocarcinoma* Carcinoid tumor Anal zone carcinoma • Mesenchymal Lesions:Gastrointestinal stromal tumors (benign or malignant)Other benign lesions Lipoma Neuroma AngiomaKaposi sarcoma • Lymphoma Morphology • Tubular adenomas: mostly tubular glands, recapitulating mucosal topology • Villous adenomas: villous projections • Tubulovillous adenomas: a mixture of the above Clinical Features • The smaller adenomas are usually asymptomatic, until such time that occult bleeding leads to clinically significant anemia. Villous adenomas are much more frequently symptomatic because of overt or occult rectal bleeding. The most distal villous adenomas may secrete sufficient amounts of mucoid material rich in protein and potassium to produce hypoproteinemia or hypokalemia. On discovery, all adenomas, regardless of their location in the alimentary tract, are to be considered potentially malignant; thus, in practical terms, prompt and adequate excision is mandated. The Adenoma-Carcinoma Sequence • The adenoma-carcinoma sequence just described accounts for about 80% of sporadic colorectal cancers. • Loss of the APC tumor suppressor gene. • Mutation of K-RAS. • 18q21 deletion. • Loss of TP53. Sessile serrated adenomas • Sessile serrated adenomas, located on the right side of the colon, may be precursors of colorectal carcinomas. • Display MSI Peutz-Jeghers polyps • Peutz-Jeghers polyps are uncommon hamartomatous polyps that occur as part of the rare autosomal dominant Peutz-Jeghers syndrome, characterized in addition by melanotic mucosal and cutaneous pigmentation. • This syndrome is caused by germ-line mutations in the LKB1 gene, which encodes a serine threonine kinase. Familial adenomatous polyposis (FAP) • Familial polyposis syndromes are uncommon autosomal dominant disorders. Their importance lies in the propensity for malignant transformation and in the insights that such transformation has provided in unraveling the molecular basis of colorectal cancer. • The genetic defect underlying FAP has been localized to the APC gene on chromosome 5q21 gastrointestinal stromal tumors (GISTs) • GISTs are now subdivided into • (a) tumors that show smooth muscle cell differentiation (the most common type); • (b) tumors with neural differentiation (often called gastrointestinal autonomic nerve tumors; • (c) tumors with smooth muscle/neural dual differentiation; • (d) tumors lacking differentiation toward these lineages. 图10-14 管状腺瘤 腺体排列紧密,细胞核增大、深染,核分裂可见 图10-15 绒毛状腺瘤 增生上皮呈指状突起,中心索由纤维组织和血管构成。表面腺上皮高级别上皮内瘤变 图10-16 锯齿状腺瘤 腺体排列紧密,腺腔不规则,锯齿状。腺上皮低级别上皮内瘤变 图10-17 家族性多发性腺瘤性息肉病 结肠布满大小不等之腺瘤性息肉,偶有正常粘膜间隔。 箭头所示之腺瘤光镜观察证实局部癌变及浸润。 图10-18 P-J息肉 息肉由分化较好的腺上皮构成大小不等的腺体和树枝状增生的平滑肌 图10-19 胃肠间质瘤 梭形瘤细胞排列成致密编织状 图10-20 胃肠间质瘤 免疫组织化学染色显示肿瘤细胞CD117(c-kit)阳性